Vevorisertib trihydrochloride

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

Vevorisertib (ARQ 751) trihydrochloride 是选择性、变构、pan-AKT 和 AKT1-E17K 突变抑制剂，可有效抑制 AKT 的磷酸化。Vevorisertib trihydrochloride 对 AKT1 和 AKT1-E17K 的 Kd 值分别为 1.2 nM 和 8.6 nM。Vevorisertib trihydrochloride 对 AKT1、AKT2 和 AKT3 的 IC50 值分别为 0.55、0.81 和 1.3 nM。 Vevorisertib trihydrochloride 可用于癌症的研究。

Vevorisertib (ARQ 751) trihydrochloride is a selective, allosteric, pan-AKT and AKT1-E17K mutant inhibitors. Vevorisertib trihydrochloride potently inhibit phosphorylation of AKT. Vevorisertib trihydrochloride has Kd values of 1.2 nM and 8.6 nM for AKT1 and AKT1-E17K, respectively. Vevorisertib trihydrochloride has IC50 values of 0.55, 0.81, and 1.3 nM for AKT1, AKT2, and AKT3, respectively. Vevorisertib trihydrochloride can be used for the research of cancer.

Vevorisertib trihydrochloride (0, 12, 33, 111, 333, 1000 nM, 2 hours) inhibits phosphorylation of AKT1-E17K.Vevorisertib trihydrochloride (1 μM for 2 hours; NIH 3T3 cells are transfected with either pcDNAAKT-WT-GFP or pcDNA-E17K-GFP) inhibits plasma membrane translocation of AKT-WT and AKT1-E17K irrespective of the presence of growth factors.Vevorisertib trihydrochloride (5 μM) exhibites 57% inhibition of full-length AKT1.Vevorisertib trihydrochloride (0, 0.012, 0.037, 0.11, 0.33, 1 μM; 2 hours) shows a dose-dependent effect on mTORC1 and AKT direct substrates including PRAS40, GSK3β, FOXO, BAD, and AS160 in cancer cell lines.Vevorisertib trihydrochloride has anti-proliferative effect on esophageal, breast, and head and neck cancer cells (GI50 < 1 μM).Vevorisertib trihydrochloride exhibits strong anti-proliferative activity in PIK3CA mutant cell lines.Vevorisertib trihydrochloride (MK-4440)/imatinib mesylate (IM) combination shows cell cycle arrest, and increases cell death of gastrointestinal stromal tumor (GIST) cells.Western Blot AnalysisCell Line:293T cells (transiently transfected with pcDNA-E17K-GFP)Concentration:0, 12, 33, 111, 333, 1000 nM Incubation Time:2 hours Result:Inhibited phosphorylation of AKT1-E17K.Western Blot Analysis Cell Line:Cancer cell lines: MDA-MB 453 (PIK3CAH1047R; Her2 amp), NCI-H1650 (PTEN null), KU-19-19 (AKT1-E17K&E49K; NRas Q61R) Concentration:0, 0.012, 0.037, 0.11, 0.33, 1 μM Incubation Time:2 hours Result: Showed a dose-dependent effect on mTORC1 and AKT direct substrates including PRAS40, GSK3β, FOXO, BAD, and AS160.

Vevorisertib trihydrochloride (25, 50 and 75 mg/kg; p.o.; 5 days dosing followed by a 4 day dosing holiday for 20 days) shows potent tumor growth inhibition of 68, 78 and 98%, respectively.Vevorisertib trihydrochloride (5, 10, 20, 40, 80, and 120 mg/kg; p.o. daily for ten days) shows tumor growth inhibition of 29, 33, 50, 73, 83, and 92%, respectively.Vevorisertib trihydrochloride reachs Cmax plasma concentrations of ≥2 μM.Vevorisertib trihydrochloride is generally well-tolerated at dose levels up to 120 mg/kg.Vevorisertib trihydrochloride (MK-4440)/IM combination shows superior efficacy in an IM-sensitive preclinical model of GIST compared with either single agent.Animal Model:Endometrial PDX mouse xenograft models (AKT1-E17K mutation tumor fragments subcutaneously implanted in athymic nude mice; tumor volume of approximately 200 mm3) Dosage:25, 50 and 75 mg/kg Administration:p.o.; 5 days dosing followed by a 4 day dosing holiday for 20 days Result:Showed potent tumor growth inhibition of 68, 78 and 98%, respectively.Animal Model:AN3CA mouse xenograft models (female NCr nu/nu mice with 250 mm3 tumors size) Dosage:5, 10, 20, 40, 80, and 120 mg/kg Administration:p.o.; daily for ten days Result:Showed tumor growth inhibition of 29, 33, 50, 73, 83, and 92%, respectively.

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Cytoskeleton/Cell Adhesion Molecules

Akt

Akt

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1416775-08-0

696.12

C35H41Cl3N8O

>98% (HPLC)

In Vitro:?DMSO 中的溶解度 : 150 mg/mL (215.48 mM; 超声助溶 ) H2O 中的溶解度 : 25 mg/mL (35.91 mM; 超声助溶 (<60°C))

Cl.Cl.Cl.CN(C1CCN(CC1)c1cccc(c1)-c1ccc2nc(-c3cccnc3N)n(-c3ccc(cc3)C3(N)CCC3)c2n1)C(C)=O

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(-20℃)

With Ice Pack

≥ 2 years